《Repressing malic enzyme 1 unbalances the redox state, redirects glucose metabolism, and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines》.pdf

Repressingmalicenzyme1redirectsglucosemetabolism， unbalancestheredoxstate，andattenuatesmigratoryand invasiveabilitiesinnasopha ngealcarcinomacelllines Fang-JingZheng，，Hao—BinYe，，，Man—SiW u，，Yi-FanLian’，，Chao-NanQian’，。 andYi-XinZeng’， Abstract Alargeamountofnicotinamideadeninedinucleotidephosphate (NADPH)isrequiredforfatryacid synthesisandmaintenanceoftheredoxstateincancercells．Malicenzyme 1(ME1)一dependentNADPH production jsoneofthe threepathwaysthatcontributetothef0rmationofthecytosolicNADPH poo1．ME1 isgenerally considered to be overexpressed in cancercellsto meetthe high demand forincreased de novofattyacidsynthesis．Inthepresentstudy，wefoundthatglucoseinducedhigherME1activityandthat repressingME1hadaprofoundimpactonglucosemetabolism ofnasopharyngealcarcinoma (NPC)cells． High incorporation ofglucoseandan enhancementofthepentosephosphatepathwaywereobserved in ME1-repressed cells．However，there were no obviouschanges in theothertwo pathways forglucose metabolism：glycolysisand oxidative phosphorylation．Interestingly，NADPH wasdecreased underlow- glucosecondition inME1一repressed cells relative to wild-type cells．whereas no significantdifferencewas observedunderhigh—glucosecondition．ME1一repressed cellshad significantly decreasedtolerance to low- glucose condition．Moreover，NADPH producedbyME1wasnotonlyimportantforfatty acid synthesisbut also essentiaIformaintenance ofthe intracellularredox stateand the protection ofcellsfrOm oxidative stress．Furthermore．diminishedmigration and invasionwere observed inME1-repressed cellsdue to a reduced IeveIofSnailprotein．Collectively，these results suggestan essentiaIrole forME1 in the productionofcytosolicNADPH andmaintenanceofmigratoryandinvasiveabilitiesofNPC cells． Keywords Nasopharyngealcarcinoma，malicenzyme 1，low glucose，NADPH Nasopharyngealcarcinoma (NPC)is a human